Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

NCT01339910 | Terminated Phase 3 Results DMC

• 5 other identifiers: BMTCTN0901U01HL069294U01HL069294-05BMT CTN 09015U24CA076518
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 32

Brief Summary

The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.

Conditions

Leukemia, Myelocytic, Acute

Keywords

Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Survival (OS)

  Overall survival is defined as survival of death from any cause.

  18 months post-randomization

Secondary Outcomes (14)

• Percentage of Participants With Relapse-Free Survival (RFS)

  18 months post-randomization

• Percentage of Participants With Disease Relapse

  18 months post-randomization

• Percentage of Participants With Treatment-related Mortality

  18 months post-randomization

• Percentage of Participants With Neutrophil and Platelet Engraftment

  Days 28 and 60 post-transplant

• Number of Participants With Donor Cell Engraftment

  Days 28 and 100 and 18 months post-transplant

Study Arms (2)

Reduced Intensity Conditioning (RIC)

EXPERIMENTAL

One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.

Drug: Fludarabine and Busulfan; Drug: Fludarabine and Melphalan

Myeloablative Conditioning Regimen (MAC)

ACTIVE COMPARATOR

One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.

Drug: Busulfan and Fludarabine; Drug: Busulfan and Cyclophosphamide; Drug: Cyclophosphamide and Total Body Irradiation

Interventions

Fludarabine and Busulfan DRUG

(Flu/Bu) * Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2) * Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4

Also known as: Fludara and Busulfex

Reduced Intensity Conditioning (RIC)

Fludarabine and Melphalan DRUG

(Flu/Mel) * Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2) * Melphalan: 140 mg/m\^2 on Day -2

Also known as: Fludara and Alkeran

Reduced Intensity Conditioning (RIC)

Busulfan and Fludarabine DRUG

(Bu/Flu) * Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2 * Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)

Also known as: Busulfex and Fludara

Myeloablative Conditioning Regimen (MAC)

Busulfan and Cyclophosphamide DRUG

(Bu/Cy) * Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4 * Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Also known as: Busulfex and Cytoxan

Myeloablative Conditioning Regimen (MAC)

Cyclophosphamide and Total Body Irradiation DRUG

(Cy/TBI) * TBI: 1200-1420 cGy on Days -7 to -4 * Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)

Also known as: Cytoxan and radiation

Myeloablative Conditioning Regimen (MAC)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal or less than 65 years old and equal to or greater than 18 years old.
• Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen enrollment.
• For patients receiving treatment of their MDS or AML prior to transplantation: a)Interval between the start of the most recent cycle of conventional cytotoxic chemotherapy and enrollment must be at least 30 days; b)Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and enrollment must be at least 10 days.
• Patients must have a related or unrelated bone marrow or peripheral blood donor who is human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.
• HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.
• Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%; b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected for hemoglobin).
• Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault formula.
• Signed informed consent.

You may not qualify if:

• Prior allograft or prior autograft.
• Symptomatic coronary artery disease.
• Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts previously detected in the cerebral spinal fluid).
• Karnofsky Performance Score less than 70.
• Patients receiving supplemental oxygen.
• Planned use of donor lymphocyte infusion (DLI) therapy.
• Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms).
• Patients seropositive for the human immunodeficiency virus (HIV).
• Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
• Females who are pregnant or breastfeeding.
• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Marrow Donor Program: collaborator

Study Sites (32)

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

University of California, San Diego Medical Center

La Jolla, California, 92093, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610-0277, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

DFCI, Brigham & Women's Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55095, United States

Location

Washington University/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Jewish Hospital BMT Program

Cincinnati, Ohio, 45236, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106-5061, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Utah BMT/University of Utah Medical School

Salt Lake City, Utah, 84132, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792-5156, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (5)

• Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellstrom-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8.

  PMID: 19357394 BACKGROUND

• Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. doi: 10.1182/blood-2005-05-2004. Epub 2005 Jun 30.

  PMID: 15994282 BACKGROUND

• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.

  PMID: 16338616 BACKGROUND

• Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, Wagner JE, Yanovich S, Kernan NA. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007 Dec;13(12):1469-76. doi: 10.1016/j.bbmt.2007.08.047.

  PMID: 18022577 BACKGROUND

• Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.

  PMID: 28380315 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

fludarabine; Busulfan; fludarabine phosphate; Melphalan; Cyclophosphamide; Whole-Body Irradiation; Radiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Physical Phenomena

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2011
• First Posted: April 21, 2011
• Study Start: June 1, 2011
• Primary Completion: January 16, 2017
• Study Completion: October 16, 2017
• Last Updated: January 4, 2023
• Results First Posted: May 30, 2018

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public.

Locations

US (32)